ABSTRACT
To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
ABSTRACT
BACKGROUND: Chinese herbs have been shown to affect osteoblasts through Wnt/β-catenin signaling pathway. Sclerostin (Sost) is an inhibitor of Wnt signaling pathway and an inhibitor of osteogenesis, and it is also an antagonistic factor that regulates the differentiation and proliferation of osteoblasts. Bushen Jianpi Huoxue decoction (BJHD) is the empirical formula in the prevention and treatment of osteoporosis at the Affiliated Orthopedics Hospital, Guangzhou University of Chinese Medicine. BJHD can promote osteogenesis and effectively treat osteoporosis. OBJECTIVE: To observe the effect of BJHD on the cell proliferation, alkaline phosphatase activity and expression levels of related proteins in Sost-overexpressed adenovirus transfected osteoblasts. METHODS: The osteoblasts were divided into two groups: blank control group (empty adenovirus transfection) and Sost overexpressed group (Sost overexpression and adenovirus transfection). Two groups were cultured with blank serum and medicine serum. The cell proliferation was tested by cell counting kit-8 assay, and alkaline phosphatase activity was tested by alkaline phosphatase kit. Expression levels of bone regulation-related proteins were tested by western blot assay. RESULTS AND CONCLUSION: Compared with the blank serum, medicine serum could increase the cell viability at 24, 48 and 72 hours in both groups (P ＜ 0.01). Compared with the blank serum, medicine serum increased the alkaline phosphatase activity (P ＜ 0.01). Compared with the blank serum, medicine serum in the blank control group decreased the expression of low-density lipoprotein receptor-related protein 5 and osteoprotegerin (P ＜ 0.01), but showed no effect on the expression of osteopontin and tumor necrosis factor α. Medicine serum in the Sost-overexpressed group decreased the expression of low-density lipoprotein receptor-related protein 5, osteoprotegerin and osteopontin, increased the expression of tumor necrosis factor α (P ＜ 0.01). These results indicate that BJHD can increase the proliferation of recombinant adenovirus transfected Sost-overexpressed osteoblasts and alkaline phosphatase activity, and regulate the expression of low-density lipoprotein receptor-related protein 5, osteoprotegerin, osteopontin, and tumor necrosis factor α.